Microsporidia are obligate intracellular parasites that affect a wide range of vertebrate and invertebrate hosts. They are recently recognized pathogens in man and are encountered almost exclusively as opportunistic infections in AIDS patients. The long term objective of this research is to identify new therapeutic modalities and drugs that will prevent, cure or ameliorate human microsporidiosis. There are two specific aims. The first goal is to validate one or more animal models for the study of drugs and combination of drugs and immunomodulators thought likely to be efficacious against these parasites in man. The second is to utilize to use human microsporidia to test the ability of antiparasitic drugs to prevent, ameliorate or cure experimentally induced microsporidial infections in vitro and in vivo. The approach consists of several phases as follows: 1) Utilize drugs for which there already is evidence of efficacy against microsporidia. At least three such drugs are known at present. 2) Use combinations of these drugs to achieve increased therapeutic or preventative efficacy. 3) Test analogues of drugs known to have at least some efficacy against the parasite in order to achieve increased efficacy and/or decreased toxicity. 4) Develop cell culture and animal model systems in which newly discovered drugs can be tested, the results of which will be reliable predictors of efficacy in human beings. 5) Use cell culture systems to gain further insight into mechanisms of drug action. This approach should result in improved therapies for the prevention and/or treatment of human microsporidiosis in AIDS patients.